The goal of this proposal is to provide mentoring for beginning clinical investigators within the framework of the principal I investigator's program of novel immunotherapeutic clinical trials. Some of the most exciting new anti-cancer therapies are based on immunologic discoveries. For example, recombinant cytokines and monoclonal antibodies are now routinely used in the setting of advanced disease, usually in combination with cytotoxic chemotherapy. Unfortunately, these regimens can be toxic, and it is not clear that combining these agents with standard chemotherapeutic drugs represents the most logical approach to their development. An alternate approach that has been employed by Dr. Carson, is the use of cytokine adjuvants to improve the efficacy of immunologic therapies. Dr. Carson's clinical program has focused on two specific areas of investigation: (1) The use of interleukin-12 and other cytokines to enhance the sensitivity of tumors to the actions of interferon-alpha; and (2). The use of cytokines to augment the immune response to an anti-HER2/neu monoclonal antibody. These trials all have evolved from basic experimental observations that were made in Dr. Carson's research laboratory. In order to, evaluate the effects of these treatments on the activity of the patient's immune system and the growth of the patient's tumor, Dr. Carson has conducted a series of novel correlative studies utilizing patient tissues. These laboratory studies have permitted a rational evaluation of the immunotherapeutic regimens and have guided the development of subsequent trials. A number of Medical and Surgical Oncology Fellows at the Ohio State University Comprehensive Cancer Center have I participated in the development and conduct of Dr. Carson's clinical trials. He has been able to train these young investigators I in many aspects of clinical research as they evaluate and treat patients enrolled in his immunotherapeutic studies. In the current proposal, Dr. Carson has outlined a detailed plan of patient-oriented research. He has also developed a systematic training program for young investigators who are involved in these clinical trials so that they will eventually be able to generate and administer protocols of their own design. In addition to their clinical research, trainees will engage in a series of educational experiences and specialized training sessions. Trainees will also attend a series of oncologic didactic sessions and will meet regularly with Dr. Carson to discuss their patients and their educational experiences. The promise of multi-institutional trials through the CALGB cooperative group insures that trainees will gain valuable experience in this aspect of clinical research. I Finally, a special emphasis has been placed on instruction relating to the ethical conduct of patient-oriented research.